国产替比培南体外杀菌及耐药性

In vitro bactericidal activity and resistant mutation of domestic tebipenem

目的评价国产替比培南对我国2009—2011年临床分离致病菌的体外杀菌作用及耐药菌产生情况。方法 53株致病菌为2009—2011年北京、济南、上海、广州、深圳、武汉、重庆、长沙和昆明9座城市的9家医院临床分离而得。替比培南的最低杀菌浓度(MBC)测定采用标准肉汤二倍稀释法,替比培南及对照抗菌药的杀菌曲线绘制及耐药研究采用菌落计数法。结果 MBC和杀菌曲线测定表明,替比培南对所测53株菌中50株菌的MBC/最低抑菌浓度(MIC)≤2,且随药物浓度升高,杀菌速率无明显提升,为时间依赖性杀菌药物。耐药频率及诱导耐药试验显示,替比培南药物浓度≥4倍MIC时,自然耐药突变频率基本≤10-8,连续14代诱导的MIC值改变不超过4倍,不易诱导产生耐药。结论国产替比培南对我国2009—2011年临床分离革兰阳性及阴性致病菌均具有很强的杀菌作用,且不易诱导产生耐药,值得进一步研究。

AIM To evaluate the in vitro bactericidal activity and resistant mutation of domestic tebipenem against clinical isolated bacteria in China from 2009 —2011. METHODS A total of 53 strains collected from 9 hospitals in Beijing, Jinan, Shanghai, Guangzhou, Shenzhen, Wuhan, Chongqing,Changsha and Kunming were involved in the study. The minimal bactericidal concentrations（ MBC） were determined by the twofold broth dilution method. Time- kills and resistance study were tested by colony form unit（CFU） count method. RESULTS The MBCs and time- kill curves showed that the specific values of MBC/MIC of tebipenem against 50 strains were ≤ 2, and there were no significant change of bactericidal rate with increased drug concentrations. So, tebipenem was a time- depended bactericidal agent. When tebipenem drug concentration ≥ 4 times MIC, the spontaneous mutant frequency ≤ 10-8. The changes of tebipenem MIC values were within 4 times MIC when srtains were sub- cultured to 14 generations in media. So, it is not easy to induce resistance against tebipenem. CONCLUSION Domestic tebipenem shows excellent bactericidal activity againstclinical isolated gram- positive and- negative bacteria in China from 2009—2011 and low induce resistance. It was deserved further study.